Primary objective:To determine the safety and tolerability of multiple doses of MOR103 in patients with active rheumatoid arthritis, at ascending dose levels.Secondary objectives:- to evaluate signs of efficacy of MOR103 in patients with active…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability of MOR103 as assessed by the safety measures.
Secondary outcome
- Change in the DAS28 score from baseline to Day 29.
- Change in the DAS28 score from basline to Day 57.
- Proportion of patients achieving ACR20, ACR50 and ACR70 response on Day 29
and Day 57.
- EULAR28 responder index on Day 29 and Day 57 (compared to baseline).
- Change in individual components of the ACR core set of measures from baseline
to Day 29 and Day 57.
- Change from baseline to Day 29 and Day 57 of the joint scoring on MRI
according to the Rheumatoid Arthritis MRI scoring system (RAMRIS) for synovitis.
- Change from baseline to Day 29 and Day 57 of the joint scoring on MRI
according to the RAMRIS for bone edema.
- Immunogenicity of MO`R103 (anti-MOR193 antibodies).
- Pharmacokinetics (PK) endpoint: MOR103 serum concentrations and PK parameters
(through levels after each dose, exposure and terminal elimination after the
last dose, accumulation and dose proportionality based on estimated AUCtau).
- Health Assessment Questionnaire (HAQ).
- SF36 health survey.
- FACIT-Fatigue: Functional Assessment of Chronic Illness Trerapy-Fatigue.
Background summary
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that
affects 0.5% to 1% of the adult population world wide. RA primarily affects the
joints and is characterized by chronic inflammation of the synovial tissue,
which eventually leads to the destruction of cartilage, bone and ligaments and
can cause joint deformity.
MOR103 is a recombinant human synthetic monoclonal antibody (mAb), IgG1 lambda,
that specifically binds to human GM-CSF and neutralises the biological function
of human GM-CSF by blocking its interaction with its cell surface receptors.
The purpose of this Phase Ib/IIa study is to evaluate the safety, preliminary
clinical activity, pharmacokinetics and immunogenicity of multiple doses of
MOR103 in patients with active RA, who are not expected to experience any
benefit from a single dose of the study drug.
Study objective
Primary objective:
To determine the safety and tolerability of multiple doses of MOR103 in
patients with active rheumatoid arthritis, at ascending dose levels.
Secondary objectives:
- to evaluate signs of efficacy of MOR103 in patients with active rheumatoid
arthritis.
- to evaluate the pharmacokinetics of multiple doses of MOR103 in patients with
active rheumatoid arthritis, at ascending dose levels, and
- to evaluate the potential immunogenicity of MOR103.
Study design
This is a multiple-dose, rising-dose study in three cohorts. Each cohort will
be double-blind and randomized. Each patient will receive a total of 4 (four)
doses, one per week on Days 1, 8, 15 and 22. Screening may occur up to 35 days
prior to dosing on Day 1 and the last visit is to be performed approximately 90
days after last dosing day (+/- 3 days). Maximum total duration for each
individual: ~ 147 days.
Intervention
Selected patients will be randomized to a treatment on Day 1 (baseline). The
study drug or placebo will be administered by slow intravenous infusion for one
hour.
Other interventions that occur during the study are:
- filling out questionnaires
- physical examination and vital signs (a.o. blood pressure and heart rate)
- blood sampling
- urine sampling
- study medication infusion
- ECG
- MRI
- Pulmonary function testing
Study burden and risks
Each patient is expected to have 12 visits for a total duration of up to 5
months. During the visits, patients will have to undergo physical examination,
blood and urine sampling, pulmonary function testing, ECG and MRI-scan. The
patients are also asked to fill out questionnaires. Study medication will be
administered by infusion, which takes about 1 hour.
The risks of treatment with MOR103 are possibility of allergic reactions such
as skin rash, swelling, breathing problems and lower blood pressure.
Additionally, the drug may provoke an immune response, which may cause the
patient to feel feverish or flu-like.
No adverse effects and no indications of the onset of an immune response were
observed in animal tests involving doses equivalent to the ones which will be
administered in this study. Theoretically. there is a possibility that the drug
may cause transient lung abnormalities in persons who are susceptible to such
conditions. In addition, there is a slight chance that the immune system may be
(partially) suppressed, which may make the patient more prone to infections.
Different single doses of MOR103 up to 3 mg/kg were administered in a Phase I
study with 63 human subjects. The most common unwanted side effects that were
mostly mild were headache and nasopharyngitis (inflammation of the nose and the
throat), dizziness and cough. Additionally, one subject experienced pneumonia
and as a consequence of the pneumonia, a septic shock as a serious side effect.
Although a possible relationship to MOR103 administration cannot be excluded,
this possibility was deemed to be low, because of other predisposing factors.
The MRI measurements in this study require the use of contrast agents that
contain the substance gadolinium. Some of these gadolinium-containing contrast
agents are suspected to be a risk for developing nephrogenic systemic fibrosis,
a rare skin disease. If the patient has normally functioning kidneys, this
possibility is very low.
For more details, see protocol page 29 and 30.
Lena-Christ-Strasse 48
82152 Martinsried/Planegg
DE
Lena-Christ-Strasse 48
82152 Martinsried/Planegg
DE
Listed location countries
Age
Inclusion criteria
- Male and female patients aged 18 years or older.
- Body Mass Index between 19.0 and 30.0 kg/m2 (extremes included)
- Diagnosis of rheumatoid arthritis (RA), according to the revised criteria of the American College of Rheumatology (ACR), 1987.
- Active disease defined as: 1. at least 3 swollen and 3 tender joints with at least 1 swollen joint involvement of the hand excluding the proximal interphalangeal (PIP) joint (using the DAS28 joint count); 2. Elevated CRP level (>= 10 mg/l); 3. Disease Activity Score "DAS28" <= 5.1.
- Functional status class I, II or III classified according to ACR 1991 revised criteria.
- Post-menopausal (for at lesat two years) or surgically sterile female patients.
- Male patients must be willing to use an effective contracteption method during the study and for at least 2 months following the completion/discontinuation of the study.
- Negative purified protein derivate (PPD) tuberculin skin test reaction or a negative tuberculosis enzyme-linked immuno sorbent assay (ELISA) test, according to the local standard practices.
Exclusion criteria
- If patients have been previously treated with anti-tumor necrosis factor alpha (TNF-α) or anti interleukin 1 (IL-1) therapy (or other biological therapy), immunosuppressive agents such as ciclosporin, mycophenolate mofetil or tacrolimus and do not comply with the following minimal washout periods prior to the first dosing of the study medication: 1. 1 month for etanercept, cilcosporin, mycophenolate mofetil, tacrolimus; 2. 2 months for adalimumab and; 3. 3 months for anakinra, infliximab and abatacept.
- Patients previously treated with rituximab.
- History of therapy with a cell depleting agent(s), including investigational agents (Campath, anti-CD3, anti-CD4, anti-CD5, anti-CD11a, anti-CD19, anti-CD22, anti-B Cell (Lymphocyte) Activating Factor antibodies [anti-Blys/BAFF]).
- Any therapy with human, chimeric or murine antibodies (other than above) or any experimental therapy within 3 months or 5 half-lives (whichever is longer) prior to screening.
- In case a patient has been discontinued from other DMARDs due to toxicity or for lack of efficacy, the time since last dose should be at least 1 month and the effects of that agent should have dissipated as indicated by the recognized duration of effect (e.g., hydroxychloroquine, sulfasalazine), or standard washout procedure (cholestyramine for leflunomide).
- Patients who received systemic steroids for other conditions (e.g. asthma), patients who received epidural steroid injections, patients who received intra-articular or systemic corticosteroid injections that were required for treatment of acute RA flare within 4 weeks before before baseline, and patients who received intra-articular injections for other conditions such as shoulder bursitis within 4 weeks.
- joint surgery within 2 months before screening.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-006129-29-NL |
| CCMO | NL28730.058.09 |